Chang Lin-Chau, Mahmood Riaz, Qureshi Samina, Breder Christopher D
Master of Science in Regulatory Science Program, Advanced Academic Programs, Krieger School of Arts and Sciences, Johns Hopkins University, Rockville, Maryland, United States of America.
School of Osteopathic Medicine, Campbell University, Lillington, North Carolina, United States of America.
PLoS One. 2017 Jun 1;12(6):e0178104. doi: 10.1371/journal.pone.0178104. eCollection 2017.
Standardised MedDRA Queries (SMQs) have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA) and Biologics License Application (BLA) submissions to the United States Food and Drug Administration (USFDA).
We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs) of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed.
A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59%) of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18%) of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated). Most searches (75% of 227 searches) with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process.
SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.
标准化医学术语集（SMQs）自21世纪初开始研发，被学术界、行业、公共卫生和政府部门用于在不良事件安全数据库中检测安全信号。本研究的目的是描述SMQs的使用方式以及对向美国食品药品监督管理局（USFDA）提交新药申请（NDA）和生物制品许可申请（BLA）的安全性分析的影响。
我们使用PharmaPendium数据库获取USFDA批准的药物和生物制品的批准摘要（SBoAs）中SMQ的使用情况。利用药物特性和SMQ使用情况来评估SMQ安全性分析在监管决策中的作用以及它们所揭示信号的准确性。
对SBoAs进行全面检索后，得到了2006年至2015年批准的184份监管提交文件。检索策略更频繁地使用带有“狭义术语”的限制性检索来提高特异性，而不是使用“广义术语”的策略来提高敏感性，同时一些检索涉及检索词的修改。1290次检索中的大多数（59%）使用了描述性统计，但其中35%使用了推断性统计。审评人员和监管人员的评论表明，1290次检索中有一小部分（18%）对监管决策有支持作用。在73份提交文件（占所调查提交文件的40%）中发现了具有监管影响的检索。大多数具有监管意义的检索（227次检索中的75%）描述了检索是如何得到确认的，这表明在决策过程中保持了谨慎。
SMQs在NDA/BLA安全性分析的呈现和审评及其监管审评中发挥着越来越重要的作用。本研究表明，SMQs最适合用于筛选过程，包括描述性统计、SMQ修改的描述以及对病例的系统验证，这对于得出监管结论至关重要。
